Papers of the Month
By Sara Mishamandani
Phthalates may negatively affect in vitro fertilization
The concentration of phthalate metabolites in urine is associated with a negative impact on in vitro fertilization (IVF) outcomes in women, according to an NIEHS-funded study. The findings link exposure to phthalates in women undergoing IVF to lower levels of the ovary cells that are necessary for reproduction, and fewer successful pregnancies and live births.
The analysis included 256 women enrolled in the Environment and Reproductive Health (EARTH) study between 2004 and 2012. Researchers measured 11 urinary phthalate metabolites, an indicator of phthalate exposure, and evaluated the association of metabolite concentrations with IVF outcomes.
The women with the highest concentrations of metabolites had a lower number of oocytes, or number of egg cells in the ovary, compared to women with the lowest levels of phthalate metabolites. The group with the lowest levels of phthalate metabolites also had more women who became pregnant and gave birth than the group with the highest urinary metabolite concentrations.
Citation: Hauser R, Gaskins AJ, Souter I, Smith KW, Dodge LE, Ehrlich S, Meeker JD, Calafat AM, Williams PL; Earth Study Team. 2015. Urinary phthalate metabolite concentrations and reproductive outcomes among women undergoing in vitro fertilization: results from the EARTH study. Environ Health Perspect; doi:10.1289/ehp.1509760 [Online 6 November 2015]
Expectant mothers near fracking wells risk adverse birth outcomes
Expectant mothers living near unconventional natural gas development, also known as fracking, in Pennsylvania were at greater risk of giving birth prematurely and having high-risk pregnancies, according to a study funded by NIEHS. The study supplements current limited evidence that unconventional natural gas development may adversely affect birth outcomes.
Researchers analyzed data from the Geisinger Health System from 2009 to 2013. Geisinger is a rural health care organization serving 40 counties in central and northeast Pennsylvania. The scientists compared pregnancy outcome with distance between pregnant women’s homes and unconventional natural gas wells. The statistical models also incorporated dates and duration of drilling during the timeframe of the pregnancies.
The researchers found that living in areas with the highest unconventional natural gas development activity was associated with a 40 percent increase in the likelihood of a woman giving birth before 37 weeks of gestation. These women also had a 30 percent increase in the chance that their pregnancy would be high-risk, a designation made by doctors based on a variety of factors, including elevated blood pressure or excessive weight gain during pregnancy.
Citation: Casey JA, Savitz DA, Rasmussen SG, Ogburn EL, Pollak J, Mercer DG, Schwartz BS. 2015. Unconventional natural gas development and birth outcomes in Pennsylvania, USA. Epidemiology; doi: 10.1097/eDe.0000000000000387 [Online 30 September 2015]
Chronic arsenic exposure may impair muscle healing after injury
Researchers, funded by NIEHS, have found that chronic exposure to arsenic may alter the ability of muscles to regenerate after injury. They also found that a protein involved in tissue repair, called NF kappa B, may play a role. According to the authors, these findings may aid in the development of strategies to prevent or reverse the effects of arsenic on muscle regeneration.
The researchers exposed mice to arsenic in their drinking water for five weeks, which compares to about two human years, then injured muscle and compared the outcomes in the exposed and unexposed mice. They found a significant decrease in muscle regeneration and functional recovery in mice exposed to arsenic. They also observed structural differences in the muscle tissue surrounding muscle cells, or extracellular matrix.
The researchers then seeded the arsenic-exposed extracellular matrix with human muscle stem cells, which are normally activated after muscle injury to restore damaged muscle tissue. They found that the arsenic-exposed extracellular matrix lowered the ability of the human stem cells to form new muscle fibers. When they blocked the activation of NF kappa B, which is activated by cellular damage and stress, the arsenic-exposed muscle recovered normally, suggesting that NF kappa B may play an important role in arsenic’s negative effects on muscle regeneration.
Citation: Zhang C, Ferrari R, Beezhold K, Stearns-Reider K, D'Amore A, Haschak M, Stolz D, Robbins PD, Barchowsky A, Ambrosio F. 2015. Arsenic promotes NF-κB-mediated fibroblast dysfunction and matrix remodeling to impair muscle stem cell function. Stem Cells; doi:10.1002/stem.2232. [Online 5 November 2015]
New tool sheds light on how environmental chemicals affect humans
NIEHS-funded researchers have developed a method, using probes, to map the reactivity of environmental chemicals across the proteome, the entire set of proteins in a body. According to the researchers, understanding the direct chemical-protein interactions of environmental chemicals may inform how molecules interact in the body and shed light on causes of disease.
By mapping the reactivity of the amino acid cysteine, they were able to show that certain environmental chemicals, including monomethylarsonous acid, a metabolite of arsenic, and pesticides such as chlorothalonil, react with a set of previously unrecognized protein targets that play key roles in metabolism.
The researchers focused on chemicals in the environment known as electrophiles, positively charged or neutral atoms or molecules that are attracted to an electron-rich site. These chemicals can react with certain regions of proteins, potentially leading to protein dysfunction and adverse health effects.
Citation: Medina-Cleghorn D, Bateman LA, Ford B, Heslin A, Fisher KJ, Dalvie EC, Nomura, DK., DK. 2015. Mapping proteome-wide targets of environmental chemicals using reactivity-based chemoproteomic platforms. Chem Biol 22(10):1394-1405.